Human umbilical cord mesenchymal stem cells derived from Wharton's jelly differentiate into insulin-producing cells in vitro

Background Islet transplantation is an effective way of reversing type Ⅰ diabetes. However, islet transplantation ishampered by issues such as immune rejection and shortage of donor islets. Mesenchymal stem cells can differentiateinto insulin-producing cells. However, the potential of human umbilical cord mesenchymal stem cells (huMSCs) tobecome insulin-producing cells remains undetermined.Methods We isolated and induced cultured huMSCs under islet cell culture conditions. The response of huMSCs weremonitored under an inverted phase contrast microscope. Immunocytochemical and immunofluorescence stainingmethods were used to measure insulin and glucagon protein levels. Reverse transcription-polymerase chain reaction(RT-PCR) was performed to detect gene expression of human insulin and PDX-1. Dithizone-staining was employed todetermine the zinc contents in huMSCs. Insulin secretion was also evaluated through radioimmunoassay.Results HuMSCs induced by nicotinamide and p-mercaptoethanol or by neurogenic differentiation 1 gene (NeuroD1)transfection gradually changed morphology from typically elongated fibroblast-shaped cells to round cells. They had atendency to form clusters. Immunocytochemical studies showed positive expression of human insulin and glucagon inthese cells in response to induction. RT-PCR experiments found that huMSCs expressed insulin and PDX-1 genesfollowing induction and dithizone stained the cytoplasm of huMSCs a brownish red color after induction. Insulin secretionin induced huMSCs was significantly elevated compared with the control group (t=6.183, P<0.05).Conclusions HuMSCs are able to differentiate into insulin-producing cells in vitro. The potential use of huMSCs in βcell replacement therapy of diabetes needs to be studied further.